The goal of our grant is to optimize the strategy of in utero transplantation of hematopoietic stem cells, with the ultimate goal of treating fetuses with congenital stem cell disorders. Our project includes transplantation of HSC into both mice and non-human primates. This year, we have continued our work with in utero transplantation of human HSCs into the fetuses of an immunodeficient mouse strain. We have observed engraftment of the cells and differentiation into multiple blood lineages, including T cells, B cells, and regulatory T cells. We are working with other HSC types, such as those derived from iPS cells, to determine whether they can engraft in these mice as well. We are also testing different routes of administration of these cells, including into the placenta, which is a site of hematopoiesis. These experiments are designed with the goal of translating these discoveries to treat fetuses with genetic disorders such as thalassemia or sickle cell disease.